Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals: Findings From the RHDGen Study.

Importance: Rheumatic heart disease (RHD), a sequela of rheumatic fever characterized by permanent heart valve damage, is the leading cause of cardiac surgery in Africa. However, its pathophysiologic characteristics and genetics are poorly understood. Understanding genetic susceptibility may aid in prevention, control, and interventions to eliminate RHD. Objective: To identify common genetic loci associated with RHD susceptibility in Black African individuals. Design, Setting, and Participants: This multicenter case-control genome-wide association study (GWAS), the Genetics of Rheumatic Heart Disease, examined more than 7 million genotyped and imputed single-nucleotide variations. The 4809 GWAS participants and 116 independent trio families were enrolled from 8 African countries between December 31, 2012, and March 31, 2018. All GWAS participants and trio probands were screened by use of echocardiography. Data analyses took place from May 15, 2017, until March 14, 2021. Main Outcomes and Measures: Genetic associations with RHD. Results: This study included 4809 African participants (2548 RHD cases and 2261 controls; 3301 women [69%]; mean [SD] age, 36.5 [16.3] years). The GWAS identified a single RHD risk locus, 11q24.1 (rs1219406 [odds ratio, 1.65; 95% CI, 1.48-1.82; P = 4.36 × 10-8]), which reached genome-wide significance in Black African individuals. Our meta-analysis of Black (n = 3179) and admixed (n = 1055) African individuals revealed several suggestive loci. The study also replicated a previously reported association in Pacific Islander individuals (rs11846409) at the immunoglobulin heavy chain locus, in the meta-analysis of Black and admixed African individuals (odds ratio, 1.16; 95% CI, 1.06-1.27; P = 1.19 × 10-3). The HLA (rs9272622) associations reported in Aboriginal Australian individuals could not be replicated. In support of the known polygenic architecture for RHD, overtransmission of a polygenic risk score from unaffected parents to affected probands was observed (polygenic transmission disequilibrium testing mean [SE], 0.27 [0.16] SDs; P = .04996), and the chip-based heritability was estimated to be high at 0.49 (SE = 0.12; P = 3.28 × 10-5) in Black African individuals. Conclusions and Relevance: This study revealed a novel candidate susceptibility locus exclusive to Black African individuals and an important heritable component to RHD susceptibility in African individuals.

Using community-led development to build health communication about rheumatic heart disease in Aboriginal children: a developmental evaluation.

OBJECTIVE: A high prevalence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) among Aboriginal children in northern Australia is coupled with low understanding among families. This has negative impacts on children's health, limits opportunities for prevention and suggests that better health communication is needed. METHODS: During an RHD echocardiography screening project, Aboriginal teachers in a remote community school created lessons to teach children about RHD in their home languages, drawing on principles of community-led development. Access to community-level RHD data, previously unknown to teachers and families, was a catalyst for this innovative work. Careful, iterative discussions among speakers of four Aboriginal languages ensured a culturally coherent narrative and accompanying teaching resources. RESULTS: The evaluation demonstrated the importance of collective work, local Indigenous Knowledge and metaphors. As a result of the lessons, some children showed new responses and attitudes to skin infections and their RHD treatment. Language teachers used natural social networks to disseminate new information. A community interagency collaboration working to prevent RHD commenced. Conclusions and implications for public health: Action to address high rates of RHD must include effective health communication strategies that value Indigenous Knowledge, language and culture, collaborative leadership and respect for Indigenous data sovereignty.

Hyperendemic rheumatic heart disease in a remote Australian town identified by echocardiographic screening.

OBJECTIVES: Using echocardiographic screening, to estimate the prevalence of rheumatic heart disease (RHD) in a remote Northern Territory town. DESIGN: Prospective, cross-sectional echocardiographic screening study; results compared with data from the NT rheumatic heart disease register. SETTING, PARTICIPANTS: People aged 5-20 years living in Maningrida, West Arnhem Land (population, 2610, including 2366 Indigenous Australians), March 2018 and November 2018. INTERVENTION: Echocardiographic screening for RHD by an expert cardiologist or cardiac sonographer. MAIN OUTCOME MEASURES: Definite or borderline RHD, based on World Heart Federation criteria; history of acute rheumatic fever (ARF), based on Australian guidelines for diagnosing ARF. RESULTS: The screening participation rate was 72%. The median age of the 613 participants was 11 years (interquartile range, 8-14 years); 298 (49%) were girls or women, and 592 (97%) were Aboriginal Australians. Definite RHD was detected in 32 screened participants (5.2%), including 20 not previously diagnosed with RHD; in five new cases, RHD was classified as severe, and three of the participants involved required cardiac surgery. Borderline RHD was diagnosed in 17 participants (2.8%). According to NT RHD register data at the end of the study period, 88 of 849 people in Maningrida and the surrounding homelands aged 5-20 years (10%) were receiving secondary prophylaxis following diagnoses of definite RHD or definite or probable ARF. CONCLUSION: Passive case finding for ARF and RHD is inadequate in some remote Australian communities with a very high burden of RHD, placing children and young people with undetected RHD at great risk of poor health outcomes. Active case finding by regular echocardiographic screening is required in such areas.

A review of outcome following valve surgery for rheumatic heart disease in Australia.

BACKGROUND: Globally, rheumatic heart disease (RHD) remains an important cause of heart disease. In Australia it particularly affects younger Indigenous and older non-Indigenous Australians. Despite its impact there is limited understanding of the factors influencing outcome following surgery for RHD. METHODS: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed to assess outcomes following surgical procedures for RHD and non-RHD valvular disease. The association with demographics, co-morbidities, pre-operative status, valve(s) affected and operative procedure was evaluated. RESULTS: Outcome of 1384 RHD and 15843 non-RHD valve procedures was analysed. RHD patients had longer ventilation, experienced fewer strokes and had more readmissions to hospital and anticoagulant complications. Mortality following RHD surgery at 30 days was 3.1% (95% CI 2.2 - 4.3), 5 years 15.3% (11.7 - 19.5) and 10 years 25.0% (10.7 - 44.9). Mortality following non-RHD surgery at 30 days was 4.3% (95% CI 3.9 - 4.6), 5 years 17.6% (16.4 - 18.9) and 10 years 39.4% (33.0 - 46.1). Factors independently associated with poorer longer term survival following RHD surgery included older age (OR1.03/additional year, 95% CI 1.01 - 1.05), concomitant diabetes (OR 1.7, 95% CI 1.1 - 2.5) and chronic kidney disease (1.9, 1.2 - 2.9), longer invasive ventilation time (OR 1.7 if greater than median value, 1.1- 2.9) and prolonged stay in hospital (1.02/additional day, 1.01 - 1.03). Survival in Indigenous Australians was comparable to that seen in non-Indigenous Australians. CONCLUSION: In a large prospective cohort study we have demonstrated survival following RHD valve surgery in Australia is comparable to earlier studies. Patients with diabetes and chronic kidney disease, were at particular risk of poorer long-term survival. Unlike earlier studies we did not find pre-existing atrial fibrillation, being an Indigenous Australian or the nature of the underlying valve lesion were independent predictors of survival.

A review of valve surgery for rheumatic heart disease in Australia.

BACKGROUND: Globally, rheumatic heart disease (RHD) remains an important cause of heart disease. In Australia it particularly affects older non-Indigenous Australians and Aboriginal Australians and/or Torres Strait Islander peoples. Factors associated with the choice of treatment for advanced RHD remain variable and poorly understood. METHODS: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed. Demographics, co-morbidities, pre-operative status and valve(s) affected were collated and associations with management assessed. RESULTS: Surgical management of 1384 RHD and 15843 non-RHD valve procedures was analysed. RHD patients were younger, more likely to be female and Indigenous Australian, to have atrial fibrillation (AF) and previous percutaneous balloon valvuloplasty (PBV). Surgery was performed on one valve in 64.5%, two valves in 30.0% and three valves in 5.5%. Factors associated with receipt of mechanical valves in RHD were AF (OR 2.69) and previous PBV (OR 1.98) and valve surgery (OR 3.12). Predictors of valve repair included being Indigenous (OR 3.84) and having fewer valves requiring surgery (OR 0.10). Overall there was a significant increase in the use of mitral bioprosthetic valves over time. CONCLUSIONS: RHD valve surgery is more common in young, female and Indigenous patients. The use of bioprosthetic valves in RHD is increasing. Given many patients are female and younger, the choice of valve surgery and need for anticoagulation has implications for future management of RHD and related morbidity, pregnancy and lifestyle plans.

Mortality attributable to rheumatic heart disease in the Kimberley: a data linkage approach.

BACKGROUND: Acute rheumatic fever (ARF) and its sequelae, rheumatic heart disease (RHD) are now uncommon in the general Australian population. However, these preventable and treatable diseases continue to affect Aboriginal Australians disproportionately, especially in remote communities. In the Kimberley region of Western Australia (WA), the prevalence of RHD is approximately 1% among Aboriginal residents. Yet an accurate and comprehensive picture of RHD-related mortality is lacking. AIM: This study aims to determine the mortality burden attributable to ARF and RHD in the Kimberley using linked hospitalisation and death registry data. METHODS: A retrospective cohort study was undertaken comprising all Kimberley residents with a WA hospital admission for ARF or RHD between 1970 and 2010, linked with the WA Death Register. We manually classified RHD-attributable deaths ('definite' or 'probable') to determine mortality burden. Hospitalisation prior to death, including valvular surgery was also ascertained. RESULTS: There were 35 RHD-attributable deaths in the Kimberley between 1990 and 2010, with 94% occurring in Aboriginal people. Their median age of death was 40 years. The age-standardised RHD annual death rate was 15.6 per 100 000 with a total of 1100 premature years of life lost before age of 75 within this group. Conventional International Classification of Diseases-generated mortality data underestimated mortality burden. CONCLUSION: RHD remains a significant cause of premature mortality for Aboriginal people in the Kimberley, with mortality rates unmatched in the general Australian population since the first half of the 20th century. Efforts to reduce progression of this disease through RHD Register and Control Programs are crucial alongside action to address underlying socioeconomic and environmental inequities.

Cardiac surgery in Indigenous Australians--how wide is 'the gap'?

BACKGROUND: Cardiovascular disease remains the leading cause of mortality in the Indigenous Australian population. Limited research exists in regards to cardiac surgery in the Aboriginal and Torres Strait Islander (ATSI) population. We aimed to investigate risk profiles, surgical pathologies, surgical management and short term outcomes in a contemporary group of patients. METHODS: Variables were assessed for 557 consecutive patients who underwent surgery at our institution between August 2008 and March 2010. RESULTS: 19.2% (107/557) of patients were of Indigenous origin. ATSI patients were significantly younger at time of surgery (mean age 54.1±13.23 vs. 63.1±12.46; p=<0.001) with higher rates of preventable risk factors. Rheumatic heart disease (RHD) was the dominant valvular pathology observed in the Indigenous population. Significantly higher rates of left ventricular impairment and more diffuse coronary artery disease were observed in ATSI patients. A non-significant trend towards higher 30-day mortality was observed in the Indigenous population (5.6% vs. 3.1%; p=0.244). CONCLUSIONS: Cardiac surgery is generally required at a younger age in the Indigenous population with patients often presenting with more advanced disease. Despite often more advanced disease, surgical outcomes do not differ significantly from non-Indigenous patients. Continued focus on preventative strategies for coronary artery disease and RHD in the Indigenous population is required.

Valvulopathies in sub-Saharan African children: patterns, humanitarian interventions and cardiac surgical problems.

Despite the high burden of rheumatic fever in sub-Saharan African, there is currently no sustained and comprehensive strategy to control the disease. Consequently in this area the number of patients affected by rheumatic valve disease (RVD), most with a surgical indication, is 10-20 fold higher than in industrialised countries and estimates indicate that more than 50% of African RVD patients will die before age 25. In this paper, we review clinical and management issues of RVD in children in sub-Saharan Africa. Severe heart failure and undergrowth are the prevalent presentation of the illness. Severe mitral regurgitation is the commonest rheumatic valvulopathy observed in the first and second decades. Valve repair, the approach of choice, may be associated with unfavourable outcomes in patients with extreme cardiomegaly. In young people, whenever correct anticoagulation may reasonably be achieved, mechanical mitral prostheses should be preferred, even in females. The early deterioration of biologic mitral prostheses strongly suggests limiting their use to those cases in which correct anticoagulation is not feasible. In most sub-Saharan countries, socioeconomic factors strongly limit access to health services and to cardiac surgery in particular. Efforts to overcome these barriers have resulted in humanitarian projects along two patterns: creation of high tech on site health care structures or transfer of children with complex diseases to receive highly specialised cardiac surgical care abroad. We summarise the experience of our programme that followed the latter approach.

Oral health of patients with severe rheumatic heart disease.

In order to determine whether adequate attention is paid to the maintenance of good oral health in patients at risk of developing infective endocarditis, we studied 44 black patients with severe rheumatic heart disease before they had cardiac surgery. Plaque and gingival index scores were calculated and panoramic radiographs were done in all patients. There were 17 males and 27 females (mean age: 30.6 years). The plaque and gingival index scores were classified as poor in 31.8 and 54.6% of patients, respectively. Panoramic radiographic findings included caries in 56.8% of patients, peri-apical pathology in 18.1% and retained roots in 22.7% of patients. This study demonstrates that inadequate attention is paid to the maintenance of good oral health in patients with severe rheumatic heart disease. The oral and dental care of patients at risk of developing infective endocarditis needs to be improved.

Cardiac surgery in the Pacific Islands.

BACKGROUND: Rheumatic heart disease constitutes a significant disease burden in under-resourced communities. Recognition of the devastating impact of rheumatic heart disease has resulted in volunteer cardiac teams from Australasia providing surgical services to regions of need. The primary objective of this study was to compare New Zealand hospitals' volunteer cardiac surgical operative results in Samoa and Fiji with the accepted surgical mortality and morbidity rates for Australasia. METHODS: A retrospective review from seven volunteer cardiac surgical trips to Samoa and Fiji from 2003 to 2009 was conducted. Patient data were retrospectively and prospectively collected. Preoperative morbidity and mortality risk were calculated using the European System for Cardiac Operative Risk Evaluation (euroSCORE). Audit data were collated in line with the Australasian Society of Cardiac and Thoracic Surgeons guidelines. RESULTS: One hundred and three operations were performed over 6 years. EuroSCORE predicted an operative mortality of 3.32%. In-hospital mortality was 0.97% and post-discharge mortality was 2.91%, resulting in a 30-day mortality of 3.88%. CONCLUSION: This study demonstrated that performing cardiac surgery in Fiji and Samoa is viable and safe. However, the mortality was slightly higher than predicted by euroSCORE. Difficulties exist in predicting mortality rates in patients with rheumatic heart disease from Pacific Island nations as known risk scoring models fail to be disease, ethnically or culturally inclusive. Audit processes and risk model development and assessment are an essential part of this complex surgical charity work and will result in improved patient selection and outcomes.

Excellent cardiac surgical outcomes in paediatric indigenous patients, but follow-up difficulties.

BACKGROUND: Indigenous Australians' infant mortality is three times that of non-Indigenous Australians. Indigenous children's mortality from rheumatic heart disease is 17-21 times that of non-Indigenous male and female children, respectively. No studies have looked specifically at the operative outcomes of cardiac surgery in paediatric Indigenous patients in Australia and little is known about their follow-up. AIMS: To describe operative outcomes of all Indigenous paediatric cardiac surgical patients at a single Australian tertiary hospital and assess their follow-up. METHODS: Database review of retrospectively collected data of all Indigenous paediatric patients who had cardiac surgery performed at The Prince Charles Hospital, Brisbane between 2002 and 2009 (112 patients, 123 operations). Follow-up was assessed by chart review and time to first post-discharge echocardiogram recorded in the hospital database. RESULTS: Eighty-one percent of operations were congenital heart disease related and 19% of operations were rheumatic heart disease related. Common co-morbidities included respiratory (9.7%) and renal dysfunction (0.8%). Common complications were, bleeding/tamponade 4.1%, cardiac arrest 4.1% and new atrial arrhythmia 2.4%. Mortality was 1% for congenital operations and 4.4% for rheumatic operations. Only 33% of patients had follow-up within eight weeks documented through letters or chart entry. Only 77.5% of patients had a documented follow-up echocardiogram. DISCUSSION: Operative outcome in Indigenous paediatric patients is similar to that found in the global literature. The follow-up for such an excellent surgical outcome has been disappointing. A coordinated action within and between health, health related and social institutions with sufficient resources will assist.

Rheumatic heart disease in indigenous populations.

Rates of acute rheumatic fever and chronic rheumatic heart disease in Aboriginal people, Torres Strait Islanders and Maori continue to be unacceptably high. The impact of rheumatic heart disease is inequitable on these populations as compared with other Australians and New Zealanders. The associated cardiac morbidity, including the development of rheumatic valve disease, and cardiomyopathy, with possible sequelae of heart failure, development of atrial fibrillation, systemic embolism, transient ischaemic attacks, strokes, endocarditis, the need for interventions including cardiac surgery, and impaired quality of life, and shortened life expectancy, has major implications for the individual. The adverse health and social effects may significantly limit education and employment opportunities and increase dependency on welfare. Additionally there may be major adverse impacts on family and community life. The costs in financial terms and missed opportunities, including wasted young lives, are substantial. Prevention of acute rheumatic fever is dependent on the timely diagnosis and treatment of sore throats and skin infections in high-risk groups. Both Australia and New Zealand have registries for acute rheumatic fever but paradoxically neither includes all cases of chronic rheumatic heart disease many of whom would benefit from close surveillance and follow-up. In New Zealand and some Australian States there are programs to give secondary prophylaxis with penicillin, but these are not universal. Surgical outcomes for patients with rheumatic valvular disease are better for valve repair than for valve replacement. Special attention to the selection of the appropriate valve surgery and valve choice is required in pregnant women. It may be necessary to have designated surgical units managing Indigenous patients to ensure high rates of surgical repair rather than valve replacement. Surgical guidelines may be helpful. Long-term follow-up of the outcomes of surgery in Indigenous patients with rheumatic heart disease is required. Underpinning these strategies is the need to improve poverty, housing, education and employment. Cultural empathy with mutual trust and respect is essential. Involvement of Indigenous people in decision making, design, and implementation of primary and secondary prevention programs, is mandatory to reduce the unacceptably high rates of rheumatic heart disease.

Surgical challenges in rheumatic heart disease in the Australian indigenous population.

BACKGROUND: Acute rheumatic fever, leading to rheumatic heart disease (RHD), is rare in Australia except amongst Aboriginal and Torres Strait Islander people. METHODS: Cardiac surgical procedures performed at Flinders Medical Centre on patients from the Top End of the Northern Territory from 1993 to 2008 were reviewed. This study compared Indigenous and non-Indigenous patients on short term morbidity and long term survival employing logistic regression and Cox proportional hazard models. We also outline the challenges of managing Aboriginal patients, as our unit services vast areas of northern Australia inhabited by Indigenous people. RESULTS: The total number of patients from the Northern Territory was 835. Amongst the Indigenous patients, there were 235 (55.6%) isolated coronary artery bypass graft procedures, 171 (40.4%) patients underwent isolated valvular surgery (91 mitral and 80 aortic), and 17 (4.0%) underwent combined valvular surgery with coronary artery bypass graft surgery. CONCLUSIONS: Aboriginal patients requiring valve surgery are younger and have greater comorbidity than non-Aboriginal people. Short term surgical results are similar to non-Aboriginal people but long term outcomes appear to be inferior. Age and socioeconomic conditions of Indigenous patients need to be considered. Cultural issues should be understood and acknowledged and surgery better focused around surgical units with appropriate infrastructure.

Association of TNFAIP3 polymorphism with rheumatic heart disease in Chinese Han population.

In a pair-matched case-control study (239 versus 478) conducted in Chinese Han population, we investigated the association between tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) gene, tumor necrosis factor receptor-associated factor 1 (TRAF1) gene, complement component 5 (C5) gene, and rheumatic heart disease (RHD). We observed no association with RHD for the five tagging single nucleotide polymorphisms (tSNP) in the C5 gene, the three tSNPs in the TNFAIP3 gene, or the two tSNPs in the TRAF1 gene. However, we determined that the tSNP, rs582757, located at intron_5 of the TNFAIP3 gene, associated with RHD in Chinese Han population. Both the distribution of genotype and allele frequencies differed significantly between case and control subjects (p = 0.001 and p = 0.0004, respectively). The minor C allele reduced the risk of RHD with a per-allele odds ratio of 0.57 (0.42-0.78) for the additive model in univariate analysis (p = 0.000). Under a dominant model, CC/CT carriers had a 0.54-fold reduced risk of RHD (95% confidence interval 0.38-0.75, p = 0.000) than TT carriers. Therefore, we report a new genetic variant (rs582757) in the TNFAIP3 gene that associated with the prevalence of RHD in Chinese Han population. Further genetic and functional studies are required to identify the etiological variants in linkage disequilibrium with this polymorphism.

High prevalence of rheumatic heart disease by clinical and echocardiographic screening among children in Fiji.

BACKGROUND AND AIM OF THE STUDY: Rheumatic heart disease (RHD) is an important cause of morbidity and mortality in young people in developing countries. Many cases of RHD are first detected when they progress to cardiac failure. Screening for RHD represents a means of detecting cases early so that preventative measures to halt the disease progression can be put into place. METHODS: A cross-sectional screening survey of RHD in 3,462 children aged 5 to 15 years in Fiji was performed in 2006. A three-stage screening method was used: stage 1 involved auscultatory screening; stage 2 was a limited echocardiography of children identified as having a suspicious murmur in stage 1; and stage 3 involved a full echocardiography of children identified as having pathology in stage 2. RESULTS: Among the 3,462 children screened, 359 (10.4%) had a significant murmur; subsequent echocardiography was performed on 331 of these children, with RHD being detected in 29 cases. The prevalence of definite RHD was 4.1 per 1,000 (95% CI 2.2-6.8), and the overall prevalence (definite or probable RHD) was 8.4 cases per 1,000 (95% CI 5.6-12). CONCLUSION: The study results suggest that there is a significant burden of undetected RHD in Fiji. The three-stage approach described here represents a practical means of screening for clinical RHD in developing countries, although it does not allow detection of the subclinical disease.

Experience with cardiac valve operations in Cape York Peninsula and the Torres Strait Islands, Australia.

OBJECTIVE: To describe the outcome of valve surgery, for rheumatic heart disease (RHD) and non-RHD, in residents of Cape York Peninsula and the Torres Strait Islands referred to the Cairns Base Hospital specialist outreach service. DESIGN AND PARTICIPANTS: Retrospective review of medical records on all patients residing in the outreach area who had surgery for valvular heart disease between 1 January 1992 and 31 December 2004. MAIN OUTCOME MEASURES: Operation type and perioperative characteristics; 5- and 10-year survival rates; reoperation rates; complications. RESULTS: Forty-seven patients met the selection criteria; the median age was 40 years (range, 4-76 years); and 39 patients were Indigenous. RHD was the predominant cause of valve dysfunction (30/47 patients). Thirty-seven patients had valve replacements, six had valve repair and four had balloon valvotomy as the initial procedure. There were three bleeding complications, two episodes of operated valve endocarditis, and six embolic complications. There were nine valve-related deaths (six in the first 5 years). At 5 years, all seven patients who had had valve repair or balloon valvotomy were alive. Seven of the 47 patients required reoperation. Survival analysis showed freedom from valve-related deaths to be 83% (95% CI, 66%-92%) at 5 years and 61% (95% CI, 33%-80%) at 10 years. Freedom from reoperation at 5 years was 88% (95% CI, 71%-95%). Among the 30 patients with RHD, freedom from valve-related death was 80% (95% CI, 60%-92%) at 5 years and 52% (95% CI, 21%-75%) at 10 years. In patients with RHD, freedom from reoperation at 5 years was 87% (95% CI, 65%-96%). CONCLUSION: Valvular heart disease results in substantial morbidity and mortality, despite intervention. Efforts need to focus on prevention of rheumatic fever and closer follow-up.

Heart disease in native Americans.

Cardiovascular disease is one of the major causes of death among native Americans. Ischemic heart disease has been relatively uncommon in the past, but this entity is rapidly becoming more frequent among Indians as a result of Western acculturation (Western high-fat diet, smoking, sedentary lifestyle). Hypertension remains a major problem in native American populations. Hypertension is often inadequately detected and treated in Indians. Rheumatic fever and rheumatic heart disease are moderately common and apparently in decline among native Americans. Finally, the fetal alcohol syndrome with its accompanying cardiac malformations is all too common among North American Indians. The amount of information available concerning cardiovascular disease in native Americans is rather small. Considerably more attention should be paid to this area in the future.